Gamma heavy chain disease: rapid, sustained response to cyclophosphamide and prednisone

A patient, CAL, with gamma heavy chain disease is presented who has had a complete remission lasting over 2 yr with combination chemotherapy consisting of pulsatile cyclophosphamide and prednisone. The patient exhibited many features of an atuoimmune process including a vasculitis, low serum complement levels, a positive antiglobulin (Coombs) test, Raynaud's phenomenon, and keratoconjunctivitis sicca. The CAL paraprotein was found to have several previously undescribed characteristics. It reacted with antisera to Fd, Fab, and Fab', suggesting that most of the Fd portion of the molecule was intace. CAL protein consists of two polypeptide chains of molecular weight 49,000 covalently linked to form a dimer of 95,000 molecular weight. The covalent linkage suggests that the hinge region of this gamma heavy chain is intact.     

Impaired interleukin-3 response in Pim-1-deficient bone marrow-derived mast cells

The mouse Pim-1 gene encodes two cytoplasmic serine-threonine-specific protein kinases. The gene has been found to be activated (overexpressed) by retroviral insertion in hematopoietic tumors in mice. Transgenic mice that overexpress Pim-1 (E mu-Pim-1) have a low incidence of spontaneous T-cell lymphomas and an increased susceptibility to Moloney murine leukemia virus and N-ethyl-N- nitrosourea-induced lymphomas. Apart from a slight enlargement of the spleen, no abnormalities were found in prelymphomatous transgenic mice. Inactivation of the Pim-1 gene in the germline of mice resulted in mice with a surprisingly subtle phenotype. Therefore, we investigated whether subtle effects of the absence of Pim-1 could be made visible during in vitro culturing of hematopoietic cells. We found that bone marrow-derived mast cells (BMMC) lacking Pim-1 had a distinct growth disadvantage when grown on interleukin (IL)-3, but not when stimulated by the factors IL-4, IL-9, or Steel factor (SF). This indicates a role for Pim-1 as a modulator of the IL-3 signal transduction pathway.     

Salient‐but‐irrelevant stimuli cause attentional capture in difficult,but attentional suppression in easy visual search

Search for a shape target is difficult when its shape is similar to the shape of the surrounding nontargets and easy when it is dissimilar. We asked whether interference from a salient but irrelevant color singleton depended on search difficulty as manipulated by target‐nontarget similarity. We found that interference was strong in difficult searches, and the occurrence of an electrophysiological index of attentional selectivity (the N2pc component) confirmed that attention was captured by the distractor. In contrast, interference from the distractor was weak with easy searches, and the occurrence of the P_D component confirmed that saliency signals from the distractor were suppressed. The results suggest that attentional suppression of salient but irrelevant distractors is only possible when search is efficient (i.e., with low target‐nontarget similarity), otherwise, attentional capture occurs. Further, we analyzed the Ppc component, a positivity occurring between 100 and 200 ms after stimulus onset contralateral to a salient feature discontinuity. It has been suggested that the Ppc reflects bottom‐up saliency signals, but we found the Ppc to occur only when the salient stimulus was unlikely to be selected, as in efficient searches. Thus, attentional requirements modulate the Ppc component.     

Elevated adenosine deaminase and purine nucleoside phosphorylase activity in peripheral blood null lymphocytes from patients with acquired immune deficiency syndrome

The purine metabolic enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) are important in lymphocyte differentiation, and genetic deficiencies of either enzyme have been associated with hereditary immunodeficiency states. Both ADA and PNP activity were measured in null cell-enriched and T cell-enriched peripheral blood lymphocytes from 16 patients with the acquired immune deficiency syndrome (AIDS), seven patients with the AIDS-related symptom complex (ARC), and seven asymptomatic homosexuals. ADA activity in nmol/10(6) lymphocytes/h was significantly elevated in null lymphocytes from AIDS (161 +/- 12) as compared with 23 healthy heterosexual controls (127 +/- 8;P less than .025). PNP activity was also significantly increased in null lymphocytes from AIDS patients (96 +/- 10;P less than .005) as well as those from ARC patients (84 +/- 11:P less than .025) relative to controls (61 +/- 5). No significant differences in enzyme activity were noted in T cell-enriched cells in any group. Along with elevated enzyme activity, AIDS patients had small yet significant increases in the percentages of HLA-DR (P less than .025), terminal deoxynucleotidyl transferase (TdT) (P less than .0001), and peanut agglutinin receptor (P less than .0001) positive lymphocytes in the null fraction compared with controls. TdT-positive cells appeared morphologically as large lymphoblasts with irregular nuclei. The data imply that the cellular immune deficiency in AIDS is not a result of deficiencies in lymphocyte ADA or PNP activity, but is more likely associated with an increase in an immature and/or activated lymphocyte subset.     

Hormone release by islet B cell-enriched and A and D cell-enriched populations prepared by flow cytometry

Dispersed pancreatic islet cells were analyzed for their low forward angle light scatter using flow cytometry. The cells produced a distinct light scatter pattern which appeared to be a function of cell size and not cell granularity. RIA of hormone content of cells collected from different regions of the pattern revealed that glucagon- and somatostatin-containing cells were concentrated in regions of lower scatter intensity and that insulin-containing cells were more numerous in regions of higher intensity. Relative to the original cell suspension, these preparations were enriched 3-fold in glucagon and somatostatin content and 6-fold in insulin content. The function of intact islets, unsorted dispersed cells, and sorted dispersed cells was examined before and after 4 days of culture. Before culture, all of the dispersed cell populations had elevated basal secretion compared with intact islets and did not respond to stimulatory concentrations of glucose, arginine, or 3-isobutyl-1-methylxanthine. After culture for 4 days, basal secretion fell, and responsiveness returned. In both the A/D cell-enriched and the B cell-enriched cultured populations, the percentage of single cells was approximately 95%. The insulin release patterns from these populations were similar to those from intact islets and unsorted dispersed cells. Glucagon release from all of the dispersed cell populations far exceeded that from intact islets. This study suggests that the structural organization of islets influences A cell function, but a clear influence upon B cell function has not been demonstrated.     

Human platelet cytoskeletons: specific content of glycolipids and phospholipids

The lipid composition of platelet cytoskeletons was analyzed. Triton X- 100 (0.5%) was used to prepare cytoskeletons from thrombin-treated platelets. The lipid/protein ratio of platelet cytoskeletons was 0.260 and the phospholipid/protein ratio was 0.177, which were comparable to the ratios present in platelets. However, there was a selective enrichment of platelet lipids in platelet cytoskeletons. Only 2 of the 5 major platelet phospholipids were detected. About 14% platelet sphingomyelin and 2% platelet phosphatidylcholine were present in platelet cytoskeletons. Only 1 of the 4 platelet neutral glycolipids, trihexosyl ceramide, was detected and was about 7% of that in intact platelets. Two percent of platelet hematoside, the predominant ganglioside in platelets, was found in cytoskeletons. Six percent of platelet cholesterol was present in platelet cytoskeletons, while no other neutral lipid could be detected. The study demonstrates that the lipid/protein ratio of platelet cytoskeletons is similar to that in platelets, but the composition of cytoskeleton lipids is specific and distinctly different from that in platelets. The selective glycolipid and phospholipid composition of cytoskeletons may be important for cytoskeleton and platelet function.     

Risk and significance of endoscopic/radiological evidence of recurrent Crohn's disease

BACKGROUND & AIMS: The aim of this study was to determine the risk of endoscopic/radiological recurrence of Crohn's disease postoperatively and the long-term outcome. METHODS: A randomized placebo-controlled trial was performed to determine the effectiveness of mesalamine in preventing recurrent Crohn's disease postoperatively. Patients in the control group were examined endoscopically/radiologically before entry into and annually during the trial. Findings were classified as minimal or severe. RESULTS: There were 76 patients (49 men and 37 women; mean age, 37.1 +/- 13.2 years). Fifty (61.7%) had terminal ileal resections. Overall, 55 endoscopic/radiological recurrences were observed in 51 patients (67.1%). Expressed actuarially, the recurrence rate was 27.5% at 1 year (95% confidence interval [CI], 15.8%-37.6%), 60.8% at 2 years (95% CI, 46%-71.3%), and 77.3% at 3 years (95% CI, 62.7%-86.3%). Nineteen (37%) were symptomatic and 12 (24%) were initially asymptomatic but later became symptomatic (mean, 13.0 +/- 8.8 months), whereas 20 (39%) remained asymptomatic (mean, 16.9 +/- 17.4 months). Patients with severe endoscopic/radiological disease were significantly more likely to be or become symptomatic than those with minimal disease (23 of 32 vs. 8 of 19, respectively; P = 0.0437). CONCLUSIONS: This study suggests that postoperative endoscopic/radiological recurrences occur later than previously reported. Furthermore, many of these patients, especially with minimal disease, will remain asymptomatic. (Gastroenterology 1997 Dec;113(6):1823-7)     

Truncal site and detoxifying enzyme polymorphisms significantly reduce time to presentation of further primary cutaneous basal cell carcinoma

Basal cell carcinoma (BCC) is the commonest cancer in Caucasians. Its incidence is rising and many patients develop multiple primary tumours at separate sites. Factors determining time between first primary tumour presentation and the next new primary lesion are unclear. We used Cox's proportional hazards model to study, in 856 Caucasians, the influence of tumour site, individual characteristics and polymorphism in glutathione S-transferase (GSTM1, GSTT1) and cytochrome P450 (CYP2D6, CYP1A1) loci on time to next primary tumour presentation. More than one tumour at first presentation (P <0.0001, hazard ratio 2.72) and GSTT1 null (P = 0.028, hazard ratio 1.74) were associated with decreased time to next primary tumour presentation. Significant two- factor interactions, corrected for number of tumours at presentation, were identified between a truncal tumour at first presentation and each of male gender, GSTM1 null and CYP2D6 EM (P <0.003, hazard ratios 3.09- 3.82). In each of these cases, all patients with the risk combination demonstrated further separate tumours within 5 years of first presentation. Thus, patients with a truncal tumour at first presentation, especially males and those presenting with more than one lesion have a significantly decreased time to presentation of further tumours and should receive more meticulous follow-up. Polymorphism in GSTM1 and CYP2D6 also influences the rate of new primary tumour accrual giving insights into the link between ultraviolet exposure and multiple tumour development.      

Pulmonary response to glass fiber by inhalation exposure.

Rats, hamsters, and guinea pigs were exposed to airborne glass fiber at a gravimetric concentration of 0.42 mg. per liter for 6 hours per day, 5 days per week for 90 days. The number of dust particles greater than 5 micron. in length was 0.73 x 10(6) per liter with an average diameter of approximately 1.2 micron. Most particles were less than 2 micron. in size and only 15% of the dust particles had a fibrous shape. Few fibers were longer than 10 micron. The pulmonary response was characterized by macrophage reaction with alveolar proteinosis at 90 days of inhalation. The light and ultrastructural alterations were similar to the other experimental or human alveolar proteinosis. The alveolar proteinosis disappeared at 1-year postexposure, but focal dust cell accumulation with proliferating granular pneumocytes persisted throughout the 2-year recovery period. No significant fibrosis or stromal changes were found in the dust-deposited areas. In hamsters and guinea pigs, most ferruginous bodies were developed from fibrous fibers but not from tiny dust particles. The tracheobronchial lymph nodes were markedly swollen and laden with dust cells.